The goal of this project is to determine whether compounds highly inhibitory to mammalian cells in culture are potentially teratogenic. To avoid complications of absorption, metabolism and excretion in whole animals, the recently established system of rodent embryo culture is used. During the initial year of this project, a mouse-breeding colony has been established to provide, on a regular basis, pregnant mice at a particular stage of gestation. Early somite-stage embryos were explanted at day 9 of gestation and cultivated in vitro for up to 48 hrs. Selected lipophilic drugs, in particular the anticonvulsants diphenylhydantoin and valproate, were added to the culture medium; their teratogenicity was assessed by anatomical and histological examinations. Developmental defects, including various neurologic and craniofacial malformation, abnormalties in body curvature, and overall growth retardation were observed when the dose of the anticonvulsant drugs was in the range of concentrations found in the plasma of treated patients.